Until the second half of the past century, cardiac tumors were diagnosed almost exclusively at autopsy. However, advances in cardiac imaging and the development of cardiopulmonary bypass made cardiac tumors treatable. Primary cardiac tumors are a rare entity with an incidence of 0.056% to 1.23% according to autopsy reports. Although patients with cardiac tumors may present with cardiovascular or constitutional symptoms, the diagnosis is frequently incidental during an imaging examination performed for a different indication. Incidental masses in the heart are more likely to be thrombi or vegetations ( Fig. 66.1 ) for which clinical correlation is paramount. If a mass is a cardiac tumor, then metastasis to the heart from a malignant process elsewhere is 30 times more common than a primary cardiac origin. Should the mass represent a primary cardiac tumor, it is likely to be benign, with myxoma being the most common primary cardiac tumor in adults and rhabdomyoma the most common in children. Primary malignant cardiac tumors are extremely rare (only 25% of the total cardiac tumors) and are generally a variety of sarcoma.
Diagnosis of Cardiac Tumors
Diagnosis of cardiac tumors may be challenging because clinical symptoms may be absent. Echocardiography is an excellent technique for imaging intracardiac disease. It provides high spatial and temporal resolution and delineates the morphology appearance, the location, and also the hemodynamic consequences. It is the optimal imaging modality for small masses (<1 cm) or masses arising from valves. Transesophageal echocardiography allows further evaluation and better characterization of questionable masses seen on transthoracic echocardiography. However, computed tomography (CT) and cardiac magnetic resonance (CMR) provide information about the characteristics of the mass and its extension. CT has better soft tissue contrast than echocardiography and can be used to definitively characterize fatty content and calcifications, which are important variables in the differential diagnosis of cardiac neoplasms. In addition, CT is faster, easier to perform, and generally has more reliable image quality. CMR more effectively depicts tumor morphology via soft tissue contrast resolution, tissue characterization, and vascularity, which makes it the most sensitive modality for detection of tumor infiltration and the best modality for characterizing tumor tissue. Both techniques provide additional valuable information, such as location of the cardiac tumor (ie, paracardiac, mural, or intracavitary), extension of the disease, presence of effusion, or presence of metastases. Biopsy of cardiac tumors is not typically warranted if operative intervention is planned because the risk of complication, particularly embolization, often outweighs the benefit of a preoperative diagnosis.
General Clinical Features
Clinical signs might be absent, and when present are more frequently related to the location of the tumor than the histology. Locally invasive cardiac masses will affect cardiac function and valve function, whereas mobile masses might lead to embolic events or even hemodynamic symptoms due to flow obstruction. Atrial masses are more likely to obstruct the atrioventricular flow, mimicking valvar stenosis, than ventricular masses obstructing the outflow tracts, which may lead to chest pain, breathlessness, or syncope. Symptoms are often markedly paradoxic and may relate to body positions. Arrhythmias are common through direct infiltration of the conduction tissue or through irritation of the myocardium itself. Atrioventricular block and ventricular tachycardia are not infrequently seen, and the initial presentation may be with sudden death. Pericardial effusion is common and is normally present in all cardiac tumors.
Diagnostic Approach
The most likely cause of a cardiac mass is a thrombus or vegetation (see Fig. 66.1 ). The final diagnosis of a cardiac mass will be obtained after its excision, but if a cardiac mass is a tumor, then a guide to its diagnosis will be obtained from the integration of clinical, demographic, histology, probable base, and location information.
In adults and children, primary benign tumors are more common than primary malignant ones. Rhabdomyoma is the most common tumor in children and myxoma is the most common in adults, representing nearly 80% of the primary cardiac tumors excised in the adult population. Elbardissi et al. reported 323 consecutive adult patients undergoing surgical resection of consecutive cardiac tumors between 1957 and 2006. Most of them were benign, 163 (50%) of these were myxomas and only 19 (6%) were primary malignant tumors. Papillary fibroelastomas were the second most common benign tumors (26%), followed by fibromas (6%) and lipomas (4%). Among the primary malignant cardiac tumors, sarcomas were the most common, followed by lymphomas. Metastatic cardiac tumors are, however, far more common than primary malignant cardiac tumors. Of patients who died of metastatic cancer, 20% have some degree of cardiac involvement, frequently asymptomatic. Spread to the heart can be via direct extension (breast, lung, esophagus, or mediastinal tumors), via arterial metastasis (melanoma, lung, breast, genitourinary or gastrointestinal tumors), via venous metastasis (renal, adrenal, thyroid, lung, or hepatic tumors), or via lymphatic metastasis (lymphoma, leukemia). The most common underlying malignancies with secondary heart involvement include lung cancer, breast cancer, lymphoma, and myeloid leukemia. Melanoma also has a predilection for the heart, with cardiac involvement present in 50% of patients with advanced disease.
Some cardiac tumors have predisposition for certain locations ( Fig. 66.2 ). Myxomas are frequently located in the left atrium, usually attached to the atrial septum. Sarcomas can also be present in the atrial septum and are frequently mistaken for a myxoma preoperatively. Angiosarcomas are more common in the right atrium, whereas rhabdomyomas and fibromas are generally located within the ventricles. Papillary fibroelastomas are normally located in the valves, and metastatic disease often affects the pericardium by direct invasion. Tumors invading the heart by venous spread will appear in the pulmonary veins or inside the vena cava, whereas tumors spreading hematologically will present within the cardiac muscle.
Treatment and Prognosis
In general, surgical resection is the treatment of choice for primary cardiac tumors in symptomatic patients. It is also recommended for patients with incidental tumors because cardiac masses might increase the risk of sudden death, embolism, obstruction, or arrhythmia. In patients with rhabdomyomas, predominantly children, most suggest that surgical intervention is only necessary in case of life-threatening symptoms because these tumors are benign and spontaneously regress with age.
Surgical strategy varies by tumor type. Cardiac myxomas arise mainly from the left atrial septum, and the surgical strategy usually includes complete tumor resection including the underlying stalk; there is an excellent long-term prognosis. However, it is difficult to suggest a unified surgical strategy for other cardiac tumors because they arise in various locations. The prognosis for other benign tumors is generally favorable with low recurrence, and quite good even if incompletely excised. Orthotopic heart transplantation is an option if tumor resection and reconstruction would be expected to cause irreparable damage to essential cardiac structures.
For malignant cardiac tumors, complete resection is often impossible because of local spread. The prognosis of patients with primary malignant cardiac tumors is very poor even if complete resection is attempted. Adjuvant chemotherapy and irradiation are usually given, but these are not effective in most cases. Favorable results of heart transplantation for primary malignant cardiac tumors have been reported despite immunosuppression.
Primary Benign Cardiac Tumors
Myxoma
Cardiac myxomas are more common in women (female-to-male ratio is 2:1) with most patients being diagnosed between the fourth and seventh decade of life. Cardiac myxomas normally originate in the left atrium (75% to 80%), from the fossa ovalis ( Fig. 66.3 ), with only one-quarter of them presenting in the right atrium. Occasionally cardiac myxomas grow through the fossa ovalis into both atria. Their pathogenesis is not well understood; some authors suggest that myxomas arise from embryonic rests that become trapped during the septation phase of cardiac development.
Cardiac myxomas normally present in isolation; however, 7% might be familial, inherited as an autosomal dominant disorder known as the Carney complex. Although the phenotype of these patients is variable, patients with Carney complex have at least two of the main features: heavy facial freckling, endocrine hyperactivity (ie, Cushing syndrome), myxomatous and nonmyxomatous endocrine neoplasia, noncardiac myxomas (typically breast and skin), and cardiac myxomas. Cardiac myxomas in this setting have an equal male-to-female ratio, are diagnosed at a younger age, are more likely to be multiple, and are likely to be found in atypical locations. Furthermore, there is a higher risk of recurrence after resection. Mutations in the PRKAR1A gene, encoding a protein kinase A regulatory subunit, appear to be responsible for up to 70% of cases of the Carney complex. It is important to differentiate Carney complex from Carney triad, which is the association of pulmonary hamartomas, extra-adrenal paragangliomas, and gastric leiomyosarcomas.
Histologically, cardiac myxomas are gelatinous and composed of scattered cells within a mucopolysaccharide stroma (see Fig. 66.3 ). Internally, they often contain cysts and areas of necrosis and hemorrhage. Calcifications are present in 16% of tumors. Cardiac myxomas are normally pedunculated and gelatinous, with a surface that can be smooth, villous, or friable. Tumors vary in size, ranging from 1 to 15 cm. Large tumors are more likely to have a smooth or gently lobulated surface and to be associated with cardiovascular symptoms, whereas friable or villous tumors are likely to present with emboli.
Clinical Manifestations
Clinical manifestation of cardiac myxomas depends on their location, size, and mobility. The most common presentation is related to cardiovascular symptoms, such as dyspnea, that normally relate to obstruction of the mitral valve inflow but also can present as sudden cardiac death. On auscultation, these patients present with signs of mitral valve obstruction, but only 15% have a “tumor plop,” which is heard as a loud but rather dull sound as the tumor prolapses into the left ventricle, and may be confused with a third heart sound. Embolization or arrhythmias are also typical presentations. In addition, cardiac myxomas may cause constitutional symptoms, similar to collagen vascular disease. Typical signs and symptoms are fever, anorexia weight loss, malaise, arthralgia, increased erythrocyte sedimentation rate and C-reactive protein, leukocytosis, thrombocytopenia, hypergammaglobulinemia, and anemia. The mechanism by which myxomas cause systemic manifestations is not fully understood; however, many myxomas produce interleukin-6, which leads to hepatic synthesis of acute-phase reactants and subsequent systemic illness.
In a series of 112 patients with cardiac myxomas, Pinede et al. reported that cardiovascular symptoms were present in 67% of patients, mainly resembling mitral valve obstruction. Evidence of systemic embolization was present in 29% of patients, 20% with neurologic deficits. Of note, despite cardiac myxomas being more frequent in women, embolic events were more common in men. Finally, constitutional symptoms were present in 34% of patients.
Diagnosis
Echocardiography is generally diagnostic in cardiac myxoma. It will define the location, size, shape, attachment, and mobility of the mass. The location in the left atrium, the characteristic narrow stalk attached to the atrial septum, and the mobility of the mass are features that allow diagnosis of a cardiac myxoma with a high degree of confidence. They may be homogeneous or have central areas of hyperlucency representing hemorrhage and necrosis. Broad-based, nonmobile myxomas may also occur, but are indeterminate at echocardiography. CT and CMR findings are variable in reflecting gross pathologic features. Because of their gelatinous nature, myxomas normally have heterogeneous low attenuation on CT. They tend to have markedly increased signal intensity on T2-weighted CMR. Contrast material enhancement in myxomas is usually heterogeneous and intense enhancement may be also seen. Nevertheless, if the mass has a typical appearance and location, CT and CMR are not necessary.
Management and Treatment
Thorough surgical resection of the tumor, including a wide resection of the myocardium at the base of the tumor stalk if possible, should be performed without delay and is considered curative. Recurrence is rare in patients with sporadic myxomas, but it can be up to 22% in those with familial myxoma syndrome. If this happens, it normally occurs in the first 4 years after resection, after which the risk of recurrence is low. Therefore, echocardiographic surveillance every 6 months has been recommended for 4 years after surgery, mainly in patients with familial myxoma syndrome.
Papillary Fibroelastoma
Papillary fibroelastoma, the second most common cardiac tumor, is a rare benign tumor affecting predominantly the cardiac valves. Because patients are often asymptomatic, the true prevalence is unknown, however, recent studies have reported a prevalence of 10%. Most are discovered incidentally in an echocardiogram. Because echocardiography is useful in older patients, the mean age of detection is 60 years, but they occur in all age groups. There is no gender preference, with a 1:1 male-to-female ratio, and there is a strong association with hypertrophic obstructive cardiomyopathy and iatrogenic factors such as surgical, radiation, and hemodynamic trauma. In contrast to sporadic cases, which are most common on cardiac valves, iatrogenic papillary fibroelastomas tend to occur in a variety of nonvalvular endocardial surfaces, usually in close proximity to the predisposing iatrogenic factor.
Histologically, papillary fibroelastomas have a superficial endothelial layer, an intermediate proteoglycans, and a central avascular core. Elastic fibers are most prominent in the core but may be absent in the distal parts of the papillae. Acute and organizing thrombi may be seen on the surface and obscure the papillary surfaces. Macroscopically, they have multiple papillary fronds attached to the endocardial surface by a short single stalk. When immersed in water, they resemble a “pom-pom” or a “sea anemone” ( Fig. 66.4 ). Papillary fibroelastomas are generally small when they develop in the cardiac chambers but their size varies from 2 to 70 mm with a mean of 9 mm. They normally appear in isolation; however, multiple tumors have been reported in 9% of patients. Papillary fibroelastomas are normally found on the cardiac valves and are more common on the ventricular side of the aortic valve followed by the atrial side of the mitral valve. Papillary fibroelastomas have been likened to Lambl excrescences, but unlike Lambl excrescences, which occur at the line of closure of semilunar valves, papillary fibroelastomas occur anywhere on the valve surface.
